Project Summary The objective of the Cancer Gene Discovery and Cancer Biology Postdoctoral Research Training Program at Cold Spring Harbor Laboratory (CSHL) is to prepare the next generation of cancer biologists to pursue independent research careers integrating cancer gene discovery with functional biology in order to facilitate the development and application of novel cancer therapeutic, diagnostic and/or preventive strategies. Features of this three-year research training program include: a combination of mandatory and elective didactic courses and seminars; structured career development guidance; graduate and community-based teaching options; and research experiences in laboratories integrated within our CSH, NCI designated Cancer Center. Cancer research opportunities span highly integrated areas that include; 1) Cancer Genetics - genetic and epigenetic progression of cancer; cancer diagnostics and experimental technology development (CRISPR/Cas, single cell analysis); 2) Cancer Gene Regulation and Cell Proliferation - splicing, RNA biology, replication, nuclear structure, transcription, tumor growth and metastasis; 3) Cancer Signal Transduction - drug sensitivity and resistance, tumor microenvironment and metastasis, immune response; and 4) Quantitative Biology- population genetics, genome structure and evolution. Postdoctoral trainees benefit from: a strong faculty to trainee ratio; a collaborative and multidisciplinary research environment; an internal Executive Committee that includes trainee representatives and an independent External Advisory Board; an on-site internationally renowned Scientific Meetings and Courses program; newly expanded state-of-the-art cancer research facilities; enhanced exposure to translational oncology as part of a new institutional partnership with Northwell Health. Over the past five years, approximately seventy-four trainees benefited from the program, of which seven trainees (three per year) were supported by the NCI T32 award, with two additional trainees being supported by combined New York State matching and CSHL institutional funding. CSHL submitted a competing T32 renewal application in 2015 requesting four positions that fell short of securing renewed NCI funding. Reviewers found the program's overall impact to be high, but noted several points and recommendations. All suggestions have been carefully evaluated and addressed in this resubmission. Program enhancements include: providing trainees with additional opportunities to understand the clinical impact of cancer and to gain an appreciation of the complexities involved in conducting and participating in clinical research; T32 trainee specific events that include training in Communicating Science to the Public; and gaining knowledge about the importance of population diversity in cancer health disparities research. Elective courses have been updated and new approaches to further enhance the diversity of program applicants and participants have begun.